The tissue lesion of the connective tissue diseases appears to be due to vascular injury induced by immune complexes. The cold precipitable immunoglobulins found in the circulation of many patients with these diseases have all the characteristics of immune complexes. Since cryoglobulins are easily isolated and quantified we propose to: 1) study their relationship to the activity and vascular complications in RA and SLE, 2) analyze those features, such as complement fixing ability, that could account for their phlogogenic capacity, 3) determine their ability to influence lymphocyte function (especially lymphocyte mediated cytotoxicity) and finally 4) to attempt to isolate antigens from SLE cryoglobulins that might be important in the pathogenesis of that disease.